IP in Movies: Extraordinary Measures (2010)

Every film is the result of the society that produced it.

Jean-Luc GodardSight and Sound, Summer 1968

Tom Vaughan · 2010 · Screenplay by Robert Nelson Jacobs, from Geeta Anand’s The Cure

The film

Extraordinary Measures follows John Crowley (Brendan Fraser), a Harvard-trained executive whose two younger children, Megan and Patrick, have Pompe disease, and Dr Robert Stonehill (Harrison Ford), the Nebraska researcher whose enzyme might save them. Crowley leaves his job, raises the money, and the two build a company around Stonehill’s idea. In outline it is true: the film is adapted from Geeta Anand’s The Cure (HarperCollins, 2006), which grew out of the Wall Street Journal reporting for which she shared the Pulitzer Prize in 2003.

The substitutions are the ordinary ones. Stonehill is a composite, drawn principally from Dr William Canfield of the University of Oklahoma Health Sciences Center. “Priozyme” is Novazyme Pharmaceuticals; “Zymagen”, the corporate acquirer, is Genzyme. What the film also replaces, and less innocently, is its own legal architecture: one scientist, one company, one race, where the record shows four programmes, a competition authority, and a right nobody in the film ever names.

Two lines of dialogue

The film puts its entire legal content into two sentences spoken by Stonehill. The first is about money.

“I don’t have the money to make my theory into a useable medicine” — Extraordinary Measures (Tom Vaughan, 2010). © CBS Films.

The second is about what he gives up in exchange for it.

“Giving them the patents to my ideas” — Extraordinary Measures (Tom Vaughan, 2010). © CBS Films.

Between them sits the economics of rare-disease research — and a mistake about which right actually does the work.

The patent race

The film needs a single laboratory. There were at least four. William Canfield is named as inventor on a series of applications filed for Novazyme between 2001 and 2004; Yuan-Tsong Chen on applications filed for Duke University from 2000; Yunxiang Zhu and Seng H. Cheng on Genzyme’s own filings; Johannes van Bree on those of Pharming Intellectual Property B.V., which was pursuing the enzyme in the milk of transgenic rabbits. The published record gives the density of it.

Date	Publication	Inventor	Applicant	Title
2003.07.03	US20030124653	William CANFIELD	Novazyme Pharmaceuticals, Inc.	Method of producing glycoproteins having reduced complex carbohydrates in mammalian cells
2003.07.03	US20030124652	William CANFIELD	Novazyme Pharmaceuticals, Inc.	Methods of producing high mannose glycoproteins in complex carbohydrate deficient cells
2005.01.06	US20050003486	William CANFIELD and Stuart KORNFELD	Novazyme Pharmaceuticals, Inc.	Expression of lysosomal hydrolase in cells expressing pro-N-acetylglucosamine-1-phosphodiester α-N-acetyl glucosimanidase
2003.07.17	US20030133924	William CANFIELD	Novazyme Pharmaceuticals, Inc.	Highly phosphorylated acid beta-glucocerebrosidase and methods of treating gaucher’s disease
2002.01.24	WO/2002/005841	Yuan-Tsong CHEN	Duke University	Treatment of glycogen storage disease type II
2011.05.05	US20110104187	Yuan-Tsong CHEN, Priya KISHNANI, and Baodong SUN	Duke University	Method of treating glycogen storage disease type III with human acid α-glucosidase
2010.01.14	WO/2010/005565	Yuan-Tsong CHEN, Priya KISHNANI, and Baodong SUN	Duke University	Method of treatment of glycogen storage disease
2010.10.07	US20100254966	Yuan-Tsong CHEN	Duke University	Treatment of glycogen storage disease type II
2005.06.09	US20050123531	Yuan-Tsong CHEN	Duke University	Treatment of glycogen storage disease type II
2002.08.15	US20020110551	Yuan-Tsong CHEN	Duke University	Treatment of glycogen storage disease type II
2008.07.24	US20080175833	Yuan-Tsong CHEN	Duke University	Treatment of glycogen storage disease type II
2003.10.23	WO/2003/086452	Yunxiang ZHU and Seng CHENG	Genzyme Corporation	Methods of enhancing lysosomal storage disease therapy
2001.01.04	EP1137762	Johannes Bernardus Mathias Marie VAN BREE, Edna Henriette Germaine VENNEKER, David P MEEKER	Genzyme Corporation	Treatment of Pompe’s disease
2009.02.04	EP2020438	Johannes Bernardus Mathias Marie VAN BREE, Edna Henriette Germaine VENNEKER, David P MEEKER	Genzyme Corporation	Treatment of Pompe’s disease
2000.06.15	WO/2000/034451	Johannes Bernardus Mathias Marie VAN BREE, Edna Henriette Germaine VENNEKER, David P MEEKER	Pharming Intellectual Property B.V.	Treatment of Pompe’s disease
2004.02.12	US20040029779	Yunxiang ZHU and Seng H. CHENG	Genzyme Corporation	Methods of enhancing lysosomal storage disease therapy by modulation of cell surface receptor density

Selected published applications on enzyme replacement therapy for lysosomal storage disorders. Source: WIPO Patentscope. The list is illustrative, not exhaustive.

The patent was not the prize

Here is what the film gets wrong, and it is worth spelling out because it is the standard misconception about pharmaceutical innovation. For a disease affecting a few thousand people, the patent is not what makes the investment rational.

The Orphan Drug Act of 1983 does that. Designation as a drug for a “rare disease or condition” — one affecting fewer than 200,000 persons in the United States (21 U.S.C. § 360bb(a)(2)) — brings a tax credit on qualified clinical testing (50% at the time of these events, reduced to 25% in 2017: 26 U.S.C. § 45C), a waiver of application fees (21 U.S.C. § 379h(a)(1)(F)) and, on approval, seven years during which the FDA may not approve another application for the same drug for the same indication (21 U.S.C. § 360cc). The European scheme is more generous: Regulation (EC) No 141/2000 gives ten years of market exclusivity (art. 8), extendable to twelve where a paediatric investigation plan is completed, for a condition affecting no more than five in ten thousand people in the Union (art. 3(1)), together with protocol assistance from the Agency (art. 6).

Patent and orphan exclusivity are not the same animal. A patent runs twenty years from filing, is earned by novelty and inventive step, blocks the making and selling of a claimed invention, and must be enforced by its owner in litigation in which it may be destroyed. Orphan exclusivity runs seven years (ten in Europe) from marketing approval, requires no invention whatever, blocks the approval of a rival rather than its sale, and is administered by the regulator without anyone going to court.

Congress understood the difference from the outset. The 1983 Act was aimed at drugs that would be “unprofitable or unpatentable”; exclusivity was extended to patentable products only by amendment in 1985. It was conceived as a substitute for the patent, not a supplement to it.

What the Federal Trade Commission saw

This is the part the film cannot show, because it happens after the credits and because it makes the hero’s company the object of the inquiry rather than its agent.

Between 1998 and 2001 Genzyme acquired control of every competing Pompe programme in the world: a joint venture with Pharming in October 1998; the rights to the Duke-derived enzyme, from Synpac, in April 2000 for US$19.5 million; and, in September 2001, Novazyme itself, for US$137.5 million in stock and up to US$87.5 million more contingent on approval. Crowley became a senior vice-president of Genzyme with responsibility for the Pompe programmes.

The Federal Trade Commission investigated the Novazyme acquisition and, on 13 January 2004, closed the file (File No. 021-0026) on a vote of three to one. Chairman Timothy Muris, for the majority, found that “the facts of this matter do not support a finding of any possible anticompetitive harm” and that the merger “more likely created benefits that will save patients’ lives”. Commissioner Mozelle Thompson dissented: the transaction brought together “the only two companies in the world researching Pompe enzyme replacement therapies” and was “a merger to monopoly in an innovation market”; he would have issued a complaint. Commissioner Pamela Jones Harbour, who declined to participate in the vote, called the decision to close “puzzling”.

What repays reading is not the outcome but one sentence of the reasoning.

The first Pompe therapy to gain FDA approval will obtain seven years of market exclusivity under the ODA. A second therapy may break that exclusivity only by establishing superiority.

That is the competitive analysis of the case, and there is no patent in it. The Commission does not ask who owns which invention. It asks who reaches the regulator first — because the first to arrive takes the market for seven years, and the second can dislodge them only by proving clinical superiority. In a rare-disease market the contested asset is a place in a queue, not a portfolio.

The epilogue proves the point

Alglucosidase alfa was authorised in the European Union on 28 March 2006 as Myozyme, and approved by the FDA on 28 April 2006. Megan and Patrick Crowley had received the enzyme three years earlier, in January 2003, in a clinical trial.

It was not Canfield’s enzyme. The approved product is the Chinese-hamster-ovary protein traceable to Chen’s cell line at Duke — the programme Genzyme had bought from Synpac — a fact the film, which needs the hero’s science to be the science that works, has no room for.

Then the patents fell. On inter partes review brought by BioMarin, the Federal Circuit in 2016 affirmed that Genzyme’s two Pompe patents, US 7,351,410 and US 7,655,226, were unpatentable as obvious; in 2017 it largely affirmed the invalidation of Duke’s US 7,056,712 on the same challenger’s petition. The patent layer around the only Pompe therapy on earth was substantially dismantled — and nothing happened. No rival enzyme came to market. The American seven years had run out in 2013 unchallenged; the European ten ran their full course, and the product was struck from the Community register of orphan medicinal products in March 2016.

The right that protected the drug was the one the film never mentions.

What the film is right about

Stonehill’s first line, though, is exactly true, and it is the more important of the two. The obstacle was never the absence of a patent. It was that nobody would pay for the work. Arnold Reuser at Erasmus University spent years looking for a company willing to fund production of the enzyme for a disease with, at best, a few thousand patients; the arithmetic did not close. Crowley’s contribution — the one the film renders faithfully — was not scientific but financial. He raised the capital that turned somebody else’s science into a medicine.

Which is why the instruments that matter in this field are fiscal and regulatory rather than proprietary: the tax credit, the fee waiver, the protocol assistance, the public programmes. The European Joint Programme on Rare Diseases, launched in January 2019 across some thirty countries, belongs to that logic and not to the patent system. So, in its way, does the orphan exclusivity itself: a monopoly granted by a health regulator to compensate for a market that is too small, which is a very different thing from a monopoly granted by a patent office to reward an invention.

Coda

John Crowley went on to lead Amicus Therapeutics and, since December 2023, the Biotechnology Innovation Organization. Extraordinary Measures ends where such films must, with the children alive.

The legal story ends elsewhere: with a monopoly the competition authority declined to undo, a set of patents a competitor destroyed at the Patent Office, and a seven-year regulatory exclusivity that quietly did all the work while the script was looking at something else.

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